Comparison of Different Treatments of Persistent Pulmonary Hypertension of the Newborn: A Systematic Review and Network Meta-Analysis

Abstract

Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disease. Despite being considered the gold standard treatment scheme, inhaled nitric oxide (iNO) is not readily available in settings with limited resources. Therefore, in recent years, research on related drugs is being actively pursued. Herein, we aimed to use random-effects network meta-analysis to evaluate the efficacy and associated mortality of different PPHN therapies. Data Sources: We electronically searched the PubMed, Embase, and Cochrane Library for data up to January 27, 2023. Study Selection: Randomized controlled trials involving neonates with PPHN assessing efficacy and mortality of various treatments. Data Extraction: Details of study population, treatments, and outcomes were extracted. Data Synthesis: Direct pairwise comparisons and a network meta-analysis was performed under random effects. The ranking probability was further assessed based on the surface under the cumulative ranking curve (SUCRA). We analyzed 23 randomized clinical trials involving 902 newborns with PPHN. Sixteen different treatment strategies were compared with each other and conventional therapy (CON). A median concentration of 10–20 parts per million (ppm) iNO (MNO) coupled with sildenafil orally administered at a dose of 1–3 mg/kg/dose every 6–8 hours (OSID) demonstrated the best efficacy (MNO + OSID vs. CON: odds ratio [OR] = 27.53, 95% CI, 2.36–321.75; SUCRA = 0.818, ranking first; moderate quality). OSID combined with milrinone administered IV also performed well in terms of efficacy (OSID + milrinone vs. CON: OR = 25.13, 95% CI = 1.67–377.78; SUCRA = 0.811, ranking second; low quality) and mortality reduction (CON vs. OSID + milrinone: OR = 25.13, 95% CI = 1.67–377.78; SUCRA = 0.786, ranking last; low quality). Conclusions: MNO + OSID is the most effective PPHN treatment. If iNO is not available, OSID + milrinone is preferred.